Katholieke Universiteit Leuven

About: Katholieke Universiteit Leuven is a education organization based out in Leuven, Belgium. It is known for research contribution in the topics: Population & Transplantation. The organization has 61109 authors who have published 176584 publications receiving 6210872 citations.

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis

Abstract: BACKGROUND Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. AIM To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. METHODS A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. RESULTS Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. CONCLUSION A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.

Toward a global view of alcohol, tobacco, cannabis, and cocaine use: Findings from the WHO world mental health surveys

Abstract: Background Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization’s (WHO’s) World Mental Health (WMH) Survey Initiative.

A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis

Abstract: Background Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease. Methods In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level. Results Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P Conclusions Obeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.).

Evaluative conditioning in humans: A meta-analysis.

Abstract: This article presents a meta-analysis of research on evaluative conditioning (EC), defined as a change in the liking of a stimulus (conditioned stimulus; CS) that results from pairing that stimulus with other positive or negative stimuli (unconditioned stimulus; US). Across a total of 214 studies included in the main sample, the mean EC effect was d = .52, with a 95% confidence interval of .466-.582. As estimated from a random-effects model, about 70% of the variance in effect sizes were attributable to true systematic variation rather than sampling error. Moderator analyses were conducted to partially explain this variation, both as a function of concrete aspects of the procedural implementation and as a function of the abstract aspects of the relation between CS and US. Among a range of other findings, EC effects were stronger for high than for low contingency awareness, for supraliminal than for subliminal US presentation, for postacquisition than for postextinction effects, and for self-report than for implicit measures. These findings are discussed with regard to the procedural boundary conditions of EC and theoretical accounts about the mental processes underlying EC.

The dead-end elimination theorem and its use in protein side-chain positioning

Abstract: The prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space¹ makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers²⁻⁵. Nonetheless, an exhaustive combinatorial search is still limited to carefully indentified packing units⁵⁶ containing a limited number of residues. For larger systems other strategies had to be developed, such as the Monte Carlo Procedure⁶⁷ and the genetic algorithm and clustering approach⁸. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains.